Post-stroke Intranasal (+)-Naloxone Delivery Reduces Microglial Activation and Improves Behavioral Recovery from Ischemic Injury

ENeuro
Jenni E AnttilaMikko Airavaara

Abstract

Ischemic stroke is the leading cause of disability, and effective therapeutic strategies are needed to promote complete recovery. Neuroinflammation plays a significant role in stroke pathophysiology, and there is limited understanding of how it affects recovery. The aim of this study was to characterize the spatiotemporal expression profile of microglial activation and whether dampening microglial/macrophage activation post-stroke facilitates the recovery. For dampening microglial/macrophage activation, we chose intranasal administration of naloxone, a drug that is already in clinical use for opioid overdose and is known to decrease microglia/macrophage activation. We characterized the temporal progression of microglia/macrophage activation following cortical ischemic injury in rat and found the peak activation in cortex 7 d post-stroke. Unexpectedly, there was a chronic expression of phagocytic cells in the thalamus associated with neuronal loss. (+)-Naloxone, an enantiomer that reduces microglial activation without antagonizing opioid receptors, was administered intranasally starting 1 d post-stroke and continuing for 7 d. (+)-Naloxone treatment decreased microglia/macrophage activation in the striatum and thalamus, promoted ...Continue Reading

Citations

Mar 15, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nguyen MaiMarc W Halterman
Jan 14, 2020·Therapeutic Delivery·John Aaron Howell, Gene L Bidwell
Jun 4, 2020·International Journal of Molecular Sciences·Chih-Cheng WuChun-Jung Chen
Apr 23, 2020·Frontiers in Neurology·Zhijuan CaoGary K Steinberg
Jul 28, 2020·International Journal of Obesity Supplements·Mauro CataldiUNKNOWN Obesity Programs of nutrition, Education, Research and Assessment (OPERA) Group
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Feb 8, 2021·CNS Drugs·Hanwool Ryan ChoiMichael M Bottros
Jan 6, 2021·International Journal of Molecular Sciences·Alexander PilozziXudong Huang
Oct 18, 2020·Brain, Behavior, and Immunity·D J DiSabato, J F Sheridan
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